Computational Study of Redox Active Centers of Blue Copper Proteins: A Computational DFT Study Matej Pavelka, J.V. Burda To cite this version: Matej Pavelka, J.V. Burda. Computational Study of Redox Active Centers of Blue Copper Proteins: A Computational DFT Study. Molecular Physics, Taylor & Francis, 2009, 106 (24), pp.2733-2748. 10.1080/00268970802672684. hal-00513245 HAL Id: hal-00513245 https://hal.archives-ouvertes.fr/hal-00513245 Submitted on 1 Sep 2010 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Molecular Physics For Peer Review Only Computational Study of Redox Active Centers of Blue Copper Proteins: A Computational DFT Study Journal: Molecular Physics Manuscript ID: TMPH-2008-0332.R1 Manuscript Type: Full Paper Date Submitted by the 07-Dec-2008 Author: Complete List of Authors: Pavelka, Matej; Charles University, Chemical Physics and Optics Burda, J.V.; Charles University, Czech Republic, Department of Chemical physics and optics DFT calculations, plastocyanin, blue copper proteins, copper Keywords: complexes URL: http://mc.manuscriptcentral.com/tandf/tmph Page 1 of 45 Molecular Physics 1 2 3 4 5 Computational Study of Redox Active Centers of Blue Copper 6 7 Proteins: A Computational DFT Study 8 9 10 11 Mat ěj Pavelka and Jaroslav V. Burda* 12 13 14 Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, 15 16 For Peer Review Only 17 Charles University, Ke Karlovu 3, 121 16 Prague 2, Czech Republic 18 19 20 *Corresponding author, e-mail: [email protected] 21 22 23 24 Abstract 25 26 27 Active sites of blue copper proteins in both reduced and oxidized states were studied 28 29 at the Density Functional Theory (DFT) level. Two families of these redox sites were 30 31 examined: the Type A centers with methionine ligand as 4 th residue and the Type B 32 33 34 with Glutamine residue. Constrained and full optimizations were performed on the 35 36 protein data bank structures in vacuo and in implicit solvent model simulating protein 37 38 and water environments. It was found that the redox sites do not possess optimum 39 40 41 geometries regardless of the oxidation state. The axial Cu-ligand bond 42 43 elongates/shortens in the fully optimized Cu(I)/Cu(II) complexes. The reduced centers 44 45 have a tendency to decrease the coordination number, while a trend to form four 46 47 48 “equivalent” bonds is preferred in the oxidized centers. Comparison of the full and 49 50 constrained optimizations also revealed that the A centers exhibit lower relaxation 51 52 53 energies. In the constrained structures, a higher ionization potential was predicted for 54 55 the A centers when compared to the B centers regardless of the influence of 56 57 environment. The calculated relative difference of the redox potentials between 58 59 60 various A and B centers is in good agreement with the experimental data. In the fully optimized complexes, the redox properties are dependent on the environment but URL: http://mc.manuscriptcentral.com/tandf/tmph Molecular Physics Page 2 of 45 1 2 3 usually higher IP for the B centers is predicted. Partial charges, MO’s, and spin 4 5 6 density distributions (obtained by natural population analysis) were analyzed together 7 8 with calculated electron paramagnetic resonance (EPR) spectra for deeper 9 10 11 understanding of the obtained results. 12 13 14 15 1. Introduction 16 For Peer Review Only 17 18 Every sixth entry in the protein data bank (PDB) contains a metal cofactor. Such 19 20 statistics demonstrate the importance of the metal ions for catalytic processes in a 21 22 23 living cell. Hence, investigation of metal sites – such as copper redox centers – is 24 25 essential for determination of molecular mechanisms in biochemistry. The Cu ions 26 27 often exhibit interesting spectral properties, which originate from the unusual 28 29 30 geometric and electronic structures that are imposed through their interactions with 31 32 protein environment. Such proteins provide many functions: electron transfer, 33 34 35 oxidation-reduction processes, oxygen transport and insertion, and so forth. 36 37 Blue copper proteins forms the so-called Type 1 Cu proteins[1,2]. These Cu 38 39 proteins have an intense absorption band near 600 nm in the oxidized Cu(II) state. 40 41 42 This transition is assigned with the S(cysteine)-Cu Ligand-to-Metal-Charge-Transfer 43 44 (LMCT). Structures of the active sites usually contain a 4-coordinated Cu ion, though 45 46 a coordination number of five was found in azurins. Structural motif consists of the 47 48 49 arrangement Cu(I)/Cu(II):(His)2CysX, where X is Met or Gln. Examples of this motif 50 51 can be found in pseudoazurin, rusticyanin, plastocyanin, mavicyanin, auracyanin, 52 53 stellacyanin, umecyanin, and amicyanin. Interestingly, reduction of the Cu(II) ion to 54 55 56 Cu(I) in type 1 proteins causes minimal structural changes. It results in a low 57 58 activation barrier for the Cu(I) →Cu(II) redox process and thus a rapid electron 59 60 2 URL: http://mc.manuscriptcentral.com/tandf/tmph Page 3 of 45 Molecular Physics 1 2 3 transfer. Very interesting review on these complexes was published recently by 4 5 6 Solomon[3]. 7 8 There is a large number of works investigating biological activity of the 9 10 11 copper proteins using both experimental and theoretical approaches. By means of UV- 12 13 VIS and EPR spectroscopy, Cu-center of azurin was studied[4]. Spectroscopic tools in 14 15 combination with DFT calculations were used to investigate the role of amino acid in 16 For Peer Review Only 17 18 axial position to the copper complex and its influence on a reduction potential[5]. 19 20 Published experimental works include a vast range of techniques, e.g. fluorescence 21 22 spectroscopy[6], X-ray absorption near-edge structure (XANES) spectra[7][8], 23 24 25 combination of EPR and electron-nuclear double resonance (ENDOR) techniques[9], 26 27 EPR and UV-VIS spectra[10], and many other. The basic aspects of a copper 28 29 coordination in the protein environment are summarized in reviews[11-14]. Charge 30 31 32 transfer (CT) dynamics of the blue copper proteins was investigated using a pump- 33 34 probe[15] and resonance Raman spectroscopy[16]. Some other experimental studies 35 36 37 dealing with these proteins should be also mentioned[17-19]. Theoretical studies of 38 39 the copper interactions with amino acids have been reported recently[20-30]. A lot of 40 41 computational effort was devoted to the examination of copper proteins[31-40]. The 42 43 44 first theoretical spectra of plastocyanin were computed by Solomon’s group[41,42] 45 46 and many studies were reported recently, e.g.[43-49]. Calculation of the EPR 47 48 parameters were published for aqua-ligated Cu(II) complexes at the modified B3LYP 49 50 51 level[50]. Similarly also azurin and some other blue copper proteins were 52 53 explored[51]. In the case of plastocyanin, QM/MM method was successfully 54 55 applied[43]. Force-field potentials were developed for Cu-ligand interactions in 56 57 58 plastocyanin[52] and applied in the study of LMCT dynamics for this protein[53]. An 59 60 analogous attempt to construct an empirical force-field for the oxidized form of blue 3 URL: http://mc.manuscriptcentral.com/tandf/tmph Molecular Physics Page 4 of 45 1 2 3 copper proteins was made earlier based on DFT calculations[54]. Same authors 4 5 6 studied coordination bonds in amicyanin and rusticyanin using QM/MM (IMOMM) 7 8 method[55]. 9 10 11 A great attention was also paid to examination of the “small inorganic 12 13 complexes” in order to determine coordination geometries and electronic properties of 14 15 various copper compounds. Investigation of these small models can provide a deeper 16 For Peer Review Only 17 18 insight into and an easier interpretation of the Cu(I)/Cu(II) behavior. Interactions of 19 20 the both Cu cations with molecules like water, ammonia, or hydrogen-sulfide were 21 22 intensively studied by many researchers[56-76]. A more detailed literature discussion 23 24 25 on this topics can be found in our previous papers where these complexes were 26 27 inspected[77-79]. 28 29 This study focuses on models of active mononuclear centers, which are 30 31 32 present in blue copper proteins (e.g. plastocyanin in Figure 1). This study gives a 33 34 comparison of electronic properties for general tetra-coordinated complexes with the 35 36 37 active centers of blue copper proteins (within the fixed-geometry from pdb 38 39 structures). 40 41 42 43 44 2. Computational Details 45 46 Active sites of the blue copper proteins (Scheme 1 ) were studied at the DFT level of 47 48 49 theory. In the Type A family of the blue proteins (with Met residue), the following 50 51 protein structures from the PDB database[80] were considered: amicyanin (1AAC), 52 53 auracyanin (1QHQ), plastocyanin (1KDI and 1KDJ), and rusticyanin (1A3Z and 54 55 56 1RCY).